Salhotra Discusses Orca-T in Phase 3 Trial for Blood Cancers

Amandeep Salhotra, MD, assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, discusses Orca-T and its evaluation in the phase 3 Precision-T trial (NCT05316701) in patients with advanced hematologic malignancies.

Orca-T is an investigational allogeneic T-cell immunotherapy that works to treat hematological malignancies, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS). According to Salhotra, Orca-T involves infusing hematopoietic stem cells and regulatory T cells on day 0, followed by conventional T cells 48 hours later.

“The idea is to give precisely controlled doses of these stem cells and conventional T cells in order to create an immune barrier, as opposed to a standard stem cell transplant in the apheresis product, where we have a mix of more than 50 different cell types,” explains Salhotra. “Some of these are helpful, like the memory T cell compartment and and the [natural killer] cell compartments, they prevent relapses, but a lot of these naive T cells are responsible for causing graft-vs-host disease. So it is kind of a mixed bag.”

The agent is currently undergoing evaluation in the phase 3 Precision-T trial.2 Findings from the study were recently presented at the 51st Annual EBMT Meeting, showing that the allogeneic immunotherapy improved moderate-to-severe chronic graft-vs-host disease (cGVHD)–free survival (cGFS) vs standard-of-care allogeneic hematopoietic stem cell transplant (allo-HSCT) in patients with advanced hematologic malignancies.

Specifically, among the 93 patients treated with Orca-T, a 1-year cGFS rate of 78.0% (95% CI, 65.0%-86.6%) was reported compared with 38.4% (95% CI, 26.2%-50.5%) in the 94 patients who underwent allo-HSCT (HR, 0.26; 95% CI, 0.14-0.47; log-rank P < .00001). In the Orca-T and allo-HSCT arms, the incidence of moderate-to-severe cGVHD was 12.6% (95% CI, 5.3%-23.1%) vs 44.0% (95% CI, 31.3%-56.1%; HR, 0.19; 95% CI, 0.08-0.43; Gray’s test P = .00002).

REFERENCE:

Meyer EH, Salhotra A, Gandhi AP, et al. Orca-T demonstrates improved survival free of chronic GvHD compared to conventional allogeneic hematopoietic stem cell transplant: a randomized phase 3 trial in advanced hematologic malignancies. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS15-01.